aia3. 
Federal Register / Vol. 58,. No. 31 / Thursday,. February 18, 1993 / Notices. 
request was published for comment in 
the Federal Register of August T9, 1992 
(57 FR 37680). 
The protocol was - reviewed and 
recommended for approval during the 
RAC meeting on September 14-15. 
1992, by a vote of 20 in favor. 0 
opposed, and no abstentions, with the 
following stipulations: (1) Submission 
of the GlIL4SvNa.25 vector sequence on 
a 3 l A inch disk to be screened for open 
reading frames that code for unwanted 
gene products, and (2) the term 
"vaccine" shouldbe deleted from the 
protocol! and informed consent 
document. 
Oa October 16, T992, Dfc Lotze 
provided the information, to ORDA. The 
data was reviewed by Drs. Lave nthal, 
DeLeon,, and Miller. Additional data 
was received from Dr. Lotze on. 
December 10. After reviewing the data, 
it was determined that it meets the 
request of the RAC The following, 
section may be added to Appendix D: 
"Appendix D-XXXTV. 
"Dr, Michael T. Lotze,. University of 
Pittsburgh, Pittsburgh, Pennsylvania, 
can conduct experiments on twenty 
patients with metastatic, and/or 
unresectable, locally advanced 
melanoma, renal cell carcinoma, breast 
cancer, or colon cancer who have failed 
standard therapy. Patients will receive- 
multiple subcutaneous injections of 
autologous tumor cells combined with 
an autologous fibroblast cell line that 
has been transduced in vitro with the 
gene coding, for Interleukin-4 (IL— 4) to 
augment the in vivo antitumor effect. 
Patients will be monitored for antitumor 
effect by PCR analysis and multiple 
biopsy of the injection site,” 
I accept this recommendation, and 
Appendix D-XXXIV of tfaeNZH 
Guidelines will be added accordingly. 
C. Addition of Appendix D-XXXV to the 
NIH. Guidelines 
In a letter dated July 17, 199-Z, Dr. 
Friedrich G. Schuenmg, Fred 
Hutchinson Cancer Research Center, 
Seattle, Washington, submitted two 
human genetransfer protocols to the 
Recombinant DNA Advisory Committee 
for formal review mid approval. The 
titles of these protocols are: fl)' 1 Phase 1/ 
IT Study of the Use of Recombinant 
Human Interleukin 3 (rhIL3j Stimulated 
Peripheral Blood Progenitor Cell 
Supplementation in Autologous Bone 
Marrow Transplantation m Patients 
with Breast Carcinoma or Hodgkin ’ s 
Disease, and (2) Evaluation of the Use 
of Recombinant Human G-CSF 
Stimulated Peripheral Blood Progenitor 
Cell Supplementation in Autologous 
Bone Marrow Transplantation in 
Patients with Lymphoid Malignancies. 
This request was published for 
comment frr the Federal Register of 
August 19, 1992 (57 FR 37580). 
These protocols were reviewed and 
recommended for approval during the 
RAC meeting on September 14—15, 
1992, by a vote of 12 in favor, 4 
opposed, and 1 abstention, with the 
notation that the Food and Drug 
Administration (FDA) will possibly 
convey revised standards ot approval 
regarding vector testing for helper virus 
contamination: The following' section 
may be added to Appendix D: 
" Appendix D-XatCV". 
"Dr. Friedrich G. Schuenmg, Fred 
Hutchinson Cancer Research Center, 
Seattle, Washington, can conduct 
human gene transfer experiments on 
patients 2r 18 years of age with breast 
cancer, Hodgkin’s disease, or non- 
Hodgkin’s lymphoma. A total of 10 
patients per year will be enrolled in the 
studies over a period of. four years. 
Patients will undergo autologous bone 
marrow transplantation with a- selected 
population of foterreukm-3- (IL— 3) or 
granulocyte colony-stimulating factor 
(G-CSF) stimulated CD34C+J peripheral 
blood repopulating cells (PBRC). that 
havebeen transduced with the gene 
coding for neomycin resistance (neo R ) 
using the- retroviral vector, LN". Patients 
will be continuously monitored for neo R 
to determine the relative contribution of 
autologous PBRCs to long-term 
hematopoietic reconstitution. 
Demon s trat io n of long-term contribution 
of autologous PBRC to hematopoiesis 
will enable the usaof PBRC alone for 
autologous transplants and suggest the 
use of PBRC as long-term carriers of 
therapeutically relevant' genes.”' 
I accept this recommendation and 
Appendix I*-XXXV of the NIH 
Guidelines will be added accordingly. 
D. Addition of Appendix D-XXXVT to 
the NIH Guidelines 
In a letter dated July 17, 1992, Dr. 
Friedrich G. Schuenmg, Fred 
Hutchinson Cancer Research Center, 
Seattle, Washington, submitted a human 
gene 1 transfer protocol to the 
Recombinant DNA Advisory- Committee 
for formal review and approval. The 
title of the protocol 1 is A Trial of G-CSF 
Stimulated 1 Peripheral Blood Stem Cells 
for Engraftmentin Identical- Twins. This 
request was published 1 for comment in 
the Federal Register of August 19, 1992 
(57 FR 37680). 
The protocol was reviewed and 
recommended for approval during' the 
RAC meeting on September 14—19, 
1992, by a vote of 11 in- favor, 2 
opposed, and 1 4 abstentions, with the 
notation that the FDA will possibly 
convey revised standards of approval 
regarding vector testing for helper virus 
contamination. The foil owing section 
may be added to Appendix D: 
"Appendix D-XXXVI. 
"Dr. Friedrich G. Schuening, Fred 
Hutchinson Cancer Research Center. 
Seattle, Washington, can conduct 
human gene transfer experiments on 
patients 218 years of age with breast 
cancer, Hodgkin's disease, or non- 
Hodgkin’s lymphoma. A total of 5 
patients- per year will 1 bo enrolled in the- 
study over a period' of four years. 
Patient? will undergo- allogeneic boner 
marrow transplant 1 with granulocyte 1 
colony-stimuiatihg factor (G-CSF)- 
stimulated CD 34(-*-)PBRC harvested 
from an identical twin, that havebeen 
transduced with nea R using, the 
retroviral 1 vector, LN 1 . Patients will be 
corrtiiruauslymnnitored forneo R to 
determine the relative contribution of 
G-CSF stimulated allogeneic PBRCs to 
long-term borre marrow engraftment. 
Demonstration of long-term contribution 
of allogeneic PBRC to hematopoiesis 
will enable the use of PBRC dona for 
allogeneic transplants and suggest the 
use of PBRC as long-term carriers of 
therapeutically relevant genes.” 
I accept this recommendation and 
Appendix EFXXXVI of the NIH 
Guidelinesvfilli be added accordingly. 
E. Addition of Appendix. D-XXXVU ta 
the NIH Guidelines 
In a letter dated June 5, 1992, Dr. 
Malcolm K. Brenner of St. Jude 
Children’s Research- Hospital, Memphis, 
Tennessee, and Dri Bonnie J. Mills of 
Baxter Healthcare Corporation-, Santa 
Ana, California-, indicated their 
intention- to submit a- human- gene 
transfer protocol to the Rbeombinant 
DNA Advisory Committee 1 fbrformaf 
review and approval.. The title of this 
protocol is: A Phase IF Trial of the 
Baxter Neuroblastoma Bone Marrow 
Purging System Using Gene Marking ta 
Assess Efficacy. This request' was 
published* for comment in the Federal 
Registerof August 19, 1992 (52 FR 
37680). 
The protocol was reviewed and 
recommended for approval during the 
RAC meeting on September 14-15, 
1992, by a vote of 19 ih favor, 0 
opposed, and no abstentions. The 
following section may be added to 
Appendix DV 
“Appendix D-XXXVIT. 
"Dr. Malcolm K. Brenner oFSt. Jude 
Children-’!* Hospital, Memphis, 
Tennessee, and Df: Bonnie* Jl Mills of 
Baxter Healthcare Corporation-, Santa 
Ana, California, can -conduct a 
multicenter uncontrolled human gene 
transfer experiment on 12 patients >21 
years of age with Stage- D- Neuroblastoma 
[ 52 ] 
Recombinant DNA Research, Volume 17 
